MULTIPLE DOSE STUDY OF SAFETY OF ABT 627

ABT 627 安全性的多剂量研究

• 批准号: 6297549
• 负责人: Michael A Carducci
• 金额: $ 0.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6297549
• 关键词: adenocarcinoma; antineoplastics; clinical research; clinical trial phase I; colon neoplasms; dosage; drug administration rate /duration; drug adverse effect; drug screening /evaluation; human subject; lung neoplasms; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; oral administration; pharmacokinetics; prostate neoplasms; renal cell carcinoma

This Phase I clinical trial to test the safety, tolerability, and pharmacokinetics of ABT-627 for patients with advanced prostate cancer (PCA) and other refractory adenocarcinomas opened to accrual in July 1997. Tumor response and changes in tumor markers are evaluated. This is a dose escalation study of ABT-627 given orally each day for 28 days, followed by a week break. If there is evidence of clinical benefit, patients may continue to receive ABT-627 therapy. Nineteen patients have been enrolled across 6 dose levels (10,20,30,45,60, 75 mg/day). The cohort (18 males, 1 female) is made up of 14 patients with PCA, 2 with renal cell cancer, 2 with colon cancer, and 1 with lung cancer. Two patients are not evaluable because of early withdrawal secondary to disease progression as evidenced by cord compression. Toxicity has been minimal, with one patient experiencing a short-lived Grade 2 headache at 20 mg/day and one other patient with a Grade 3 headache for 4-5 days. Nasal congestion is the most frequent complaint. No hematologic, hepatic, or renal toxicity has been noted in the treated patients. Early pharmacokinetics are consistent with those obtained from healthy volunteers. The agent has a half-life of nearly 25 hours. Three patients with narcotic requiring pain had improvement in their pain with either a reduction in pain ratings or a decrease in narcotic use (Dose levels 10, 20, 30 mg/day) during the study period. One patient in this small cohort had a PSA decline < 50%, with the remaining PCA patients having PSA stabilization or minor declines. Of the 19 patients, 4 remain on study, 2 were withdrawn early, 4 patients progressed after 28 days of therapy, and 9 patients received therapy on the extension trial. Accrual continues to go exceedingly well. In summary, ABT-627, an ETA endothelin-receptor antagonist, is well tolerated in patients with advanced adenocarcinoma. Early PSA responses in the patients with prostate cancer and improvement in bone pain with a concomitant decrease in narcotic use is encouraging. Phase II studies with this agent are underway at this institution and other centers nationally and internationally. This Phase I trial laid the foundation for this accelerated program of drug development.

该阶段I临床试验以测试安全性，耐受性和 晚期前列腺癌患者的ABT-627药代动力学 （PCA）和其他难治性腺癌于7月开放为应计 1997。评估肿瘤反应和肿瘤标记的变化。 这 是每天口服ABT-627的剂量升级研究28天， 然后休息一周。 如果有临床益处的证据， 患者可能会继续接受ABT-627治疗。 十九位患者 已在6剂水平（10,20,30,45,60，75 mg/天）中招募。 该队列（18名男性，1名女性）由14例PCA患者组成，2例 患有肾细胞癌，2个结肠癌，1例肺癌。 两名患者因继发于继发的早期戒断而无法评估 疾病进展如绳索压缩所证明。 毒性已经存在 最小 以20毫克/天的速度，另一位患有3级头痛的患者持续4-5天。 鼻充血是最常见的抱怨。 没有血液学， 治疗患者已经注意到肝或肾毒性。 早期的药代动力学与从健康中获得的药物一致 志愿者。 代理人的半衰期近25小时。 三 患有疼痛的麻醉性患者的疼痛有所改善 疼痛等级的降低或麻醉量减少（剂量） 在研究期间，10、20、30 mg/天）。 其中一个患者 小队列的PSA下降<50％，其余PCA患者 具有PSA稳定或较小的下降。 在19例患者中，有4例 继续研究，早期撤回2例，28岁后有4例患者进展 治疗的天数和9名患者在延长试验中接受了治疗。 应计的进展非常好。总而言之，ABT-627，ETA 内皮素受体拮抗剂，患有 晚期腺癌。 患者的早期PSA反应 前列腺癌和骨痛的改善，并随之减少 在麻醉品中，令人鼓舞的是。 使用该药物的第二阶段研究是 该机构和其他全国其他中心正在进行中 国际。 这阶段I试验为此奠定了基础 加速药物开发计划。